George Cotsonis

Chronic alcohol abuse is associated with an increased incidence of acute respiratory distress syndrome and severity of multiple organ dysfunction in patients with septic shock.

ObjectiveAlcohol is one of the most commonly used drugs in the world and causes dysfunction in many vital organs. However, the effects of chronic alcohol abuse on acute lung injury and nonpulmonary organ dysfunction are relatively unexplored. The goal of this study was to determine the effects of chronic alcohol abuse on the incidence and severity of the acute respiratory distress syndrome and multiple organ dysfunction syndrome in patients with septic shock. DesignMulticenter prospective epidemiologic study. SettingIntensive care units of four university urban hospitals. PatientsA total of 220 critically ill patients with septic shock. Measurements and Main FindingsThirty percent of the patients (66 of 220) were identified as having a history of chronic alcohol abuse based on a positive response to an alcohol screening questionnaire. The incidence of acute respiratory distress syndrome in patients with a positive history of chronic alcohol abuse was 70% (46 of 66), compared with 31% (47 of 154) in individuals without a history of chronic alcohol abuse (p < .001). After adjusting for differences in the source of infection, sex, age, chronic hepatic dysfunction, diabetes, severity of illness, nutritional status, and smoking status, the effects of chronic alcohol abuse on the incidence of acute respiratory distress syndrome remained significant (p < .001; odds ratio, 3.70; 95% confidence interval, 1.83–7.71). The effect of the source of infection (pulmonary vs. nonpulmonary) on the development of acute respiratory distress syndrome also remained significant in this multivariable analysis (p < .001; odds ratio, 3.68; 95% confidence interval, 1.95–7.18). Based on the highest daily Sequential Organ Failure Assessment score, patients with a history of chronic alcohol abuse had more severe nonpulmonary organ dysfunction when compared with nonalcoholics (9.42 ± 3.89 vs. 8.05 ± 4.10, p = .01). After adjusting for source of infection, sex, age, nutritional status, history of diabetes, and smoking status, the effects of chronic alcohol abuse on the incidence of nonpulmonary organ dysfunction also remained significant (p = .03; odds ratio, 2.07; 95% confidence interval, 1.09–3.97). ConclusionsWe conclude that chronic alcohol abuse is an independent risk factor for acute respiratory distress syndrome and increases the severity of nonpulmonary organ dysfunction in patients with septic shock.

Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression

Angiogenesis and lymphangiogenesis are essential for breast cancer progression and are regulated by vascular endothelial growth factors (VEGF). To determine clinical and molecular correlates of these processes, we measured blood and lymphatic vascular microvessel density in 29 invasive carcinomas (22 ductal, six lobular, one papillary), using the vascular marker CD31 and the novel lymphatic marker D2-40. Microvessel density was assessed microscopically and by image cytometry, and was compared with tumor histology, grade, stage, lymph node metastasis, hormone receptors, HER2/neu status, and expression of VEGF, VEGF-C and VEGF-D by immunohistochemistry or quantitative RT-PCR. Strong correlation was observed between visual and image cytometric microvessel density using D2-40 but not CD31 (P=0.016 and 0.1521, respectively). Image cytometric CD31 microvessel density correlated with tumor size, grade, stage and lymph node metastasis (P=0.0001, 0.0107, 0.0035 and 0.0395, respectively). D2-40 microvessel density correlated with tumor stage (P=0.0123 by image cytometry) and lymph node metastasis (P=0.0558 by microscopy). Immunohistochemical VEGF signal in peritumoral blood vessels correlated with image cytometric CD31 and D2-40 microvessel density (P=0.022 and 0.0012, respectively), consistent with the role of VEGF in blood and lymphatic vascular growth. Intratumoral VEGF-C and VEGF-D expression by quantitative RT-PCR correlated with D2-40 (P=0.0291 by image cytometry) but not with CD31 microvessel density, which could suggest a selective role of VEGF-C and VEGF-D in lymphangiogenesis. CD31 and D2-40 microvessel density correlated significantly with several prognostic factors, including lymph node metastasis. Thus, measurements of angiogenesis and lymphangiogenesis may have utility for breast cancer pathology, particularly for estimation of metastatic risk.

Collaterals dramatically alter stroke risk in intracranial atherosclerosis

Stroke risk due to intracranial atherosclerosis increases with degree of arterial stenosis. We evaluated the previously unexplored role of collaterals in modifying stroke risk in intracranial atherosclerosis and impact on subsequent stroke characteristics.

Prophylactic balloon angioplasty fails to prolong the patency of expanded polytetrafluoroethylene arteriovenous grafts: results of a prospective randomized study.

PURPOSE Maintenance of hemodialysis access grafts represents an enormous social and clinical problem. Current grafts and graft salvage techniques are inadequate. Consequently, there has been increasing interest in the use of minimally invasive catheter techniques to prophylactically treat stenoses in functioning arteriovenous grafts. Prophylactic balloon angioplasty has been widely suggested as prolonging assisted primary patency. We have performed a prospective randomized trial to compare patients who underwent percutaneous transluminal angioplasty (PTA) for graft stenoses > 50% with a control group that received no intervention. Our hypothesis was that to be efficacious a minimal benefit of 20% prolongation in patency would be necessary. METHODS Color flow duplex scanning was used to detect > 50% stenoses in functioning expanded polytetrafluoroethylene grafts. Patients were then subjected to confirmatory angiographic evaluation. Those who had angiographic stenoses > 50% were randomized to balloon angioplasty or observation. Patients were followed-up with duplex scanning every 2 months. Statistical analysis was performed using the Kaplan-Meier technique. Although demographically the patient groups were well matched, there were more prior interventions and concurrent central stenoses in the treatment group. Outcomes were graft thrombosis, graft dysfunction that precluded dialysis, and six or more PTA procedures within 18 months. RESULTS In the treatment and observation groups, the 6-month patency rates were 69% +/- 7% and 70% +/- 7%, respectively. The 12-month patency rates for the treatment and observation groups were 51% +/- 6% and 47% +/- 4%, respectively. There was no significant difference between these two groups (p = 0.97), with an 80% confidence limit for detection of a difference greater than 20%. CONCLUSIONS This study demonstrates that a generic approach of PTA to treat all polytetrafluoroethylene grafts with stenoses > 50% does not prolong patency and cannot be supported.

Risk factor status and vascular events in patients with symptomatic intracranial stenosis

Background: There are limited data on the relationship between control of vascular risk factors and vascular events in patients with symptomatic intracranial arterial stenosis. Methods: We utilized the Warfarin Aspirin Symptomatic Intracranial Disease study database to analyze vascular and lifestyle risk factors at baseline and averaged over the course of the trial. Cutoff levels defining good control for each factor were prespecified based on national guidelines. Endpoints evaluated included 1) ischemic stroke, myocardial infarction, or vascular death or 2) ischemic stroke alone. Univariate associations were assessed using the log-rank test and multivariable analysis was done using Cox proportional hazards regression. Results: From baseline until year 2 follow-up, there was not a significant improvement in blood pressure control. During the same period, there were improvements in patients with total cholesterol <200 mg/dL (54.6% to 79.2%, p < 0.001) or low-density lipoprotein <100 mg/dL (28.7% to 55.9%, p < 0.001). Multivariable analysis showed that systolic blood pressure ≥140 mm Hg (HR = 1.79, p = 0.0009, 95% confidence limits 1.27 to 2.52), no alcohol consumption (HR 1.69, 1.21 to 2.39, p = 0.002), and cholesterol ≥200 mg/dL (HR 1.44, 1.004 to 2.07, p = 0.048) were associated with an increased risk of stroke, myocardial infarction, or vascular death. The same risk factors were predictors of ischemic stroke alone in multivariable analysis. Conclusions: Elevated blood pressure and cholesterol levels in symptomatic patients with intracranial stenosis are associated with an increased risk of stroke and other major vascular events.

Time course of regression of left ventricular hypertrophy in treated hypertensive patients

Abstract In a prospective study, 32 hypertensive patients with echocardiographic evidence of left ventricular hypertrophy were treated with methyldopa, hydrochlorothiazide, or methyldopa and hydrochlorothiazide combined. Echocardiograms and electrocardiograms were obtained in each of the 32 patients before treatment, at the point of initial blood pressure control, and then one, three, and six months thereafter; in 27 patients these studies were also obtained after 12 and 18 months. Left ventricular end-diastolic posterior wall thickness decreased in seven patients whose blood pressure was controlled with methyldopa alone (p

The Infant Aphakia Treatment Study: Design and Clinical Measures at Enrollment

OBJECTIVE To compare the use of contact lenses and intraocular lenses (IOLs) for the optical correction of unilateral aphakia during infancy. METHODS In a randomized, multicenter (12 sites) clinical trial, 114 infants with unilateral congenital cataracts were assigned to undergo cataract surgery with or without IOL implantation. Children randomized to IOL treatment had their residual refractive error corrected with spectacles. Children randomized to no IOL treatment had their aphakia treated with a contact lens. MAIN OUTCOME MEASURES Grating acuity at 12 months of age and HOTV visual acuity at 4 1/2 years of age. APPLICATION TO CLINICAL PRACTICE This study should determine whether either treatment for an infant with a visually significant unilateral congenital cataract results in a better visual outcome. RESULTS Enrollment began December 23, 2004, and was completed January 16, 2009. The median age at the time of cataract surgery was 1.8 months. Fifty patients were 4 to 6 weeks of age at the time of enrollment; 32, 7 weeks to 3 months of age; and the remaining 32, more than 3 to less than 7 months of age. Fifty-seven children were randomized to each treatment group. Eyes with cataracts had shorter axial lengths and steeper corneas on average than the fellow eyes. CONCLUSIONS The optimal optical treatment of aphakia in infants is unknown. However, the Infant Aphakia Treatment Study was designed to provide empirical evidence of whether optical treatment with an IOL or a contact lens after unilateral cataract surgery during infancy is associated with a better visual outcome.

Quality-of-life changes and psychiatric and neurocognitive outcome after heart and liver transplantation

A prospective study compared psychiatric, neurocognitive, and quality-of-life changes of heart and liver transplant patients. The 51 heart and 61 liver transplant candidates and recipients completed the Beck depression inventory (BDI), state-trait anxiety inventory (STAI), sickness impact profile (SIP), mini-mental state (MMS), California verbal learning test (CVLT), Wisconsin card sorting test (WCST), trailmaking test (TMT), and the impact message inventory (IMI). Data were gathered before transplant and at 3-month intervals for up to 1 year after transplant. Psychometric tests scores were correlated with electroencephalograms for the liver patients. Both groups showed significant improvements after transplant in neurocognitive functioning, depressive symptoms, and quality of life.

Design, Progress and Challenges of a Double-Blind Trial of Warfarin versus Aspirin for Symptomatic Intracranial Arterial Stenosis

Background and Relevance: Atherosclerotic stenosis of the major intracranial arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the 900,000 patients who suffer a TIA or stroke each year in the USA, intracranial stenosis is responsible for approximately 10%, i.e. 90,000 patients. There have been no prospective trials evaluating antithrombotic therapies for preventing recurrent vascular events in these patients. The main objective of this trial is to compare warfarin [International Normalized Ratio (INR) 2–3] with aspirin (1,300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients presenting with TIA or stroke caused by stenosis of a major intracranial artery. Study Design: Prospective, randomized, double-blind, multicenter trial. The sample sizerequired will be 403 patients per group, based on stroke and vascular death rates of 33% per 3 years in the aspirin group vs. 22% per 3 years in the warfarin group, a p value of 0.05, power of 80%, a 24% rate of ‘withdrawal of therapy’, and a 1% rate of ‘lost to follow-up’. Conduct of Trial: Patients with TIA or nondisabling stroke caused by ≧50% stenosis of a major intracranial artery documented by catheter angiography are randomized to warfarin or aspirin. Patients are contacted monthly by phone and examined every 4 months until a common termination date. Mean follow-up in the study is expected to be 3 years. Conclusion: This study will determine whether warfarin or aspirin is superior for patients with symptomatic intracranial arterial stenosis. Furthermore, it will identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high to justify a subsequent trial comparing intracranial angioplasty/stenting with best medical therapy in this subset of patients.

Exercise testing and training in physically disabled men with clinical evidence of coronary artery disease

Abstract A prospective, randomized, controlled clinical trial in patients with coronary artery disease (CAD) and a concurrent physical disability evaluated the effects of a home exercise training program on cardiovascular function and blood lipids. Eighty-eight men between the ages of 42 and 72 years (mean 62) with documented CAD and a physical disability with functional use of ≥2 etremities including 1 arm were randomized to either a 6-month home exercise training program using wheelchair ergometry or to a control group that received usual and customary care. Both groups received dietary instructions and were requested to follow a fat-controlled diet. Exercise test variables with echocardiography and blood lipids were measured at baseline and at 6 months. The home exercise training group significantly improved both peak exercise left ventricular ejection fraction (p = 0.007) and fractional shortening (p = 0.01) between baseline to 6 months, whereas the control group showed no significant changes. Exercise training effects of decreased resting heart rate (p = 0.03) and decreased peak rate pressure product (p = 0.03) were also found in the treatment group. No exercise-related cardiac complications occurred. Both groups significantly (p ≤ 0.01) increased high-density lipoprotein cholesterol levels. These results indicate that physically disabled men with CAD can safely participate in a home exercise training program which may result in intrinsic cardiac benefits. The metabolic cost of activities of daily living imposed on this disabled popu lation may also have a positive effect on high-density lipoprotein cholesterol levels.